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LIV-1 promotes prostate cancer epithelial-to-mesenchymal transition and metastasis through HB-EGF shedding and EGFR-mediated ERK signaling
- Source :
- PLoS ONE, PLoS ONE, Vol 6, Iss 11, p e27720 (2011)
- Publication Year :
- 2011
-
Abstract
- LIV-1, a zinc transporter, is an effector molecule downstream from soluble growth factors. This protein has been shown to promote epithelial-to-mesenchymal transition (EMT) in human pancreatic, breast, and prostate cancer cells. Despite the implication of LIV-1 in cancer growth and metastasis, there has been no study to determine the role of LIV-1 in prostate cancer progression. Moreover, there was no clear delineation of the molecular mechanism underlying LIV-1 function in cancer cells. In the present communication, we found increased LIV-1 expression in benign, PIN, primary and bone metastatic human prostate cancer. We characterized the mechanism by which LIV-1 drives human prostate cancer EMT in an androgen-refractory prostate cancer cells (ARCaP) prostate cancer bone metastasis model. LIV-1, when overexpressed in ARCaP(E) (derivative cells of ARCaP with epithelial phenotype) cells, promoted EMT irreversibly. LIV-1 overexpressed ARCaP(E) cells had elevated levels of HB-EGF and matrix metalloproteinase (MMP) 2 and MMP 9 proteolytic enzyme activities, without affecting intracellular zinc concentration. The activation of MMPs resulted in the shedding of heparin binding-epidermal growth factor (HB-EGF) from ARCaP(E) cells that elicited constitutive epidermal growth factor receptor (EGFR) phosphorylation and its downstream extracellular signal regulated kinase (ERK) signaling. These results suggest that LIV-1 is involved in prostate cancer progression as an intracellular target of growth factor receptor signaling which promoted EMT and cancer metastasis. LIV-1 could be an attractive therapeutic target for the eradication of pre-existing human prostate cancer and bone and soft tissue metastases.
- Subjects :
- Male
Non-Clinical Medicine
Tumor Physiology
lcsh:Medicine
Soft Tissue Neoplasms
Mesodermal Cells
Signal transduction
ERK signaling cascade
Metastasis
Prostate cancer
Mice
Oxidative Damage
0302 clinical medicine
Molecular cell biology
RNA interference
Basic Cancer Research
Genitourinary Cancers
Signaling in Cellular Processes
Membrane Receptor Signaling
Neoplasm Metastasis
lcsh:Science
Extracellular Signal-Regulated MAP Kinases
Cation Transport Proteins
0303 health sciences
Multidisciplinary
Evidence-Based Medicine
Chemistry
Prostate Cancer
Prostate Diseases
Bone metastasis
virus diseases
Signaling cascades
Neoplasm Proteins
ErbB Receptors
Gene Expression Regulation, Neoplastic
Matrix Metalloproteinase 9
Oncology
030220 oncology & carcinogenesis
Disease Progression
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinase 2
Medicine
Oncology Agents
Cellular Types
Ncam
Heparin-binding EGF-like Growth Factor
Research Article
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Urology
Bone Neoplasms
Signaling Pathways
Antibodies
03 medical and health sciences
Growth factor receptor
Cancer stem cell
Internal medicine
Cell Line, Tumor
medicine
Cell Adhesion
Cancer Detection and Diagnosis
Early Detection
Animals
Humans
Epithelial–mesenchymal transition
Biology
030304 developmental biology
lcsh:R
Cancer
Prostatic Neoplasms
Cancers and Neoplasms
Epithelial Cells
medicine.disease
Genitourinary Tract Tumors
Endocrinology
HEK293 Cells
Cancer cell
Cancer research
lcsh:Q
Gene expression
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....1316d32057241e7094ac357ac8a36a00